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  • Review Article
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Treatment of pulmonary arterial hypertension with targeted therapies

Nature Reviews Cardiology volume 8, pages 526–538 (2011)Cite this article

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Abstract

Pulmonary arterial hypertension (PAH) is a rare disorder characterized by progressive obliteration of the pulmonary microvasculature that results in elevated pulmonary vascular resistance and premature death. Although no cure exists for PAH, improved understanding of the pathobiological mechanisms of this disease has resulted in the development of effective therapies that target specific aberrant pathways. Agents that modulate abnormalities in the prostacyclin, endothelin, and nitric oxide pathways have been shown in randomized, controlled studies to confer improvements in functional status, pulmonary hemodynamics, and possibly even slow disease progression. Several additional pathways believed to play an important role in the pathogenesis of PAH have been identified as potentially useful therapeutic targets and a number of investigative approaches focusing on these targets are in active development. In this Review, we highlight the pharmacological agents currently available for the treatment of PAH and discuss potential novel strategies.

Key Points

  • Pulmonary arterial hypertension is a complex, rapidly progressive, and incurable disease

  • The past decade has witnessed a remarkable increase in the number of available treatments for pulmonary arterial hypertension that can confer meaningful improvements in important clinical end points

  • Currently licensed therapies for pulmonary arterial hypertension target abnormalities in the endothelin, prostacyclin, and nitric oxide signaling pathways

  • Escalation of therapy using combination regimens is recommended for patients with pulmonary arterial hypertension who continue to exhibit evidence of disease progression

  • Progress in basic and clinical research on pulmonary arterial hypertension has led to improved understanding of disease pathogenesis and identification of a host of novel therapeutic targets

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Figure 1: Treatment algorithm for pulmonary arterial hypertension.
Figure 2: Current and emerging targets and therapies for pulmonary arterial hypertension.

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Authors and Affiliations

  1. Université Paris-Sud, Faculté de Médecine, Le Kremlin-Bicêtre F-94276; Service de Pneumologie, Hôpital Antoine Béclère, AP-HP, Clamart, F-92140

    Dermot S. O'Callaghan, Laurent Savale, David Montani, Xavier Jaïs, Olivier Sitbon, Gérald Simonneau & Marc Humbert

  2. INSERM U999, Centre Chirurgical Marie Lannelongue, Le Plessis-Robinson, F-92350, France

    Dermot S. O'Callaghan, Laurent Savale, David Montani, Xavier Jaïs, Olivier Sitbon, Gérald Simonneau & Marc Humbert

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  1. Dermot S. O'Callaghan
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Contributions

D. S. O'Callaghan, L. Savale, and M. Humbert researched data for the article. D. S. O'Callaghan, L. Savale, D. Montani, X. Jaïs, G. Simonneau, and M. Humbert contributed to the discussion of content. The article was written by D. S. O'Callaghan. All authors reviewed and edited the manuscript before submission.

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Correspondence to Marc Humbert.

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Competing interests

L. Savale has received honoraria from Actelion, Novartis, and Pfizer. D. Montani has received honoraria from Actelion, Bayer–Schering, GlaxoSmithKline, Lilly, Novartis, Pfizer, and United Therapeutics and has received research support from Actelion and Novartis. X. Jaïs has received honoraria from Actelion, GlaxoSmithKline, Lilly, and Pfizer. O. Sitbon has acted as a consultant for and has received honoraria and research support from Actelion, GlaxoSmithKline, Lilly, Pfizer, and United Therapeutics. He has also received honoraria and research support from Bayer–Schering and research support from Novartis. Both G. Simonneau and M. Humbert have acted as consultants for and have received honoraria and research support from Actelion, Bayer–Schering, GlaxoSmithKline, Lilly, Novartis, Pfizer, and United Therapeutics. D. S. O'Callaghan declares no competing interests.

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O'Callaghan, D., Savale, L., Montani, D. et al. Treatment of pulmonary arterial hypertension with targeted therapies. Nat Rev Cardiol 8, 526–538 (2011). https://doi.org/10.1038/nrcardio.2011.104

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